This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background and Aims Evidence is accumulating that obesity increases the risk of colon cancer but the underlying molecular mechanisms are not well known. Oxidative stress appears to be a major factor in this process. We hypothesize that colon carcinogenesis will be affected by uncoupling protein-2 (UCP2), a mitochondrial anion carrier involved in producing reactive oxygen species (ROS). To critically test this hypothesis, we are using in vitro and in vivo experimental paradigms. In addition, we are evaluating the correlation between UCP2 expression in human-derived colon cancer and various tumor markers and factors involved in colon carcinogenesis. Development and growth of sporadic colon cancer, a cause of significant mortality in the US, is greatly affected by intracellular levels of reactive oxygen species (ROS). Mitochondria are the primary source of ROS. Uncoupling protein-2 (UCP2) controls mitochondrial ROS production and reduces oxidative stress, but the relevance of this ability to the biology of cancer cells remains unclear. It is hypothesized that UCP2 modulates the initiation and progression of colon cancer. This project was terminated in Jan. 2006 after a competitive review of 12 RFAs. (see Program Evaluation Report section) Dr. Baffy received a "transition award" from Rhode Island Hospital to support 6 months of research.